Expert Systems Celebrates Milestone in Clinical Development of Lonitoclax, a Best-in-Class BCL-2 Inhibitor, Developed in Partnership with Lomond Therapeutics

ROCKVILLE, Md., Dec. 17, 2024 /PRNewswire/ -- Expert Systems, a leader in AI-powered drug discovery, proudly celebrates the promising clinical results of oral once-daily lonitoclax, a next-generation BCL-2 inhibitor developed in collaboration with Lomond Therapeutics. The results of the single ascending dose Phase 1 studies demonstrate important advantages of lonitoclax over venetoclax and venetoclax-like molecules for chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), and potentially other oncology indications.

Lonitoclax demonstrated no significant safety signals at exposures sufficient to achieve robust inhibition of BCL-2, as measured via ex vivo activation of caspase in primary CLL cells. Importantly, the co-administration of itraconazole—a potent CYP 3A4 inhibitor—did not significantly alter lonitoclax exposures. These results highlight a key differentiation from venetoclax and similar molecules, which require complex dose titration and ritonavir co-administration, and emphasize important advantages in safety, tolerability, and feasibility of outpatient treatment.

"Lonitoclax's promising Phase 1 results highlight the strength of our AI-enabled platform in driving the development of next-generation therapies," said Bill Farley, Chief Business Officer at Expert Systems. "Our platform de-risks early-stage drug development by reducing time and costs while delivering data-driven insights to optimize safety and efficacy. We are proud to support Lomond Therapeutics in advancing this innovative BCL-2 inhibitor, which has the potential to transform the treatment landscape for CLL and AML patients."

About Lonitoclax

Lonitoclax is a next generation BCL-2 inhibitor that has demonstrated best-in-class molecular pharmacology with the highest selectivity against BCL2, a key pro-survival protein that is overexpressed in many cancers. To mitigate the hematologic and immune toxicities observed with venetoclax, lonitoclax was designed with a unique binding mode to improve selectivity for BCL-2 over BCL-XL. In addition, a shorter half-life and reduced P4503A4 inhibition properties were built into the molecule to mitigate tumor lysis syndrome and drug accumulation risk, respectively. Lonitoclax has demonstrated monotherapy activity in pre-clinical models, as well as synergistic activity when combined with azacitidine, FLT3 inhibitors, and menin inhibitors in AML xenograft models. Unlike venetoclax, lonitoclax had minimal immunosuppressive activity on B cells, CD8 T cells, and NK cells in preclinical models.

About Expert Systems

Expert Systems, Inc., an advanced accelerator platform, is equipped with a comprehensive, hybrid AI-based system that covers the entire spectrum of preclinical drug discovery and early development phases. This includes target identification, virtual screening, non-clinical and clinical pharmacology, chemical liability assessment, and toxicology. Utilizing a unique combination of proprietary and public databases, Expert Systems employs specialized software tools to evaluate the intellectual property landscape and construct a competitive drug intelligence strategy to de-risk candidate selection for rapid transition from in silico to first-in-human trials. Expert Systems has been pivotal in establishing Seed and Series A companies, organizing and managing over 30 research and development programs across various financial investors and strategic partners in North America, Europe, and Australia. To learn more visit www.expertsystems.inc

Media Contact:

Bill Farley
CBO
[email protected]

SOURCE Expert Systems, Inc.